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Process for preparing an alpha-lipoic acid/cyclodextrin complex and product prepared

a technology of cyclodextrin and alpha-lipoic acid, which is applied in the field of process for preparing an alpha-lipoic acid/cyclodextrin complex and product preparation, can solve the problems of large amount of water needed to solubilize cyclodextrin, yellow powder and unstable light, and poor solubility in water, so as to reduce the cost of the production process in a rapid and simple manner

Inactive Publication Date: 2006-06-22
WACKER CHEM GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a simple and efficient process for preparing a cyclodextrin / alpha-lipoic acid complex. This process involves dissolving alpha-lipoic acid and cyclodextrin in an alkaline solution, followed by the addition of acid to lower the pH. The resulting mixture of solids in water contains the desired complex without the need for high temperatures or long mixing times. This process reduces production costs and allows for the formation of the complex in a more convenient manner.

Problems solved by technology

It is a yellowish powder and is unstable in light.
Its solubility in water is very poor.
On use of the solution method on the production scale, the amount of water needed to solubilize the cyclodextrin is enormous.
For economic reasons, therefore, these methods cannot be used commercially to prepare a cyclodextrin / alpha-lipoic acid complex.
Elevated temperatures can have a negative impact on the stability of the alpha-lipoic acid.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of a Cyclodextrin Alpha-Lipoic Acid Alpha Cyclodextrin Complex

[0025] 117.2 g of a 45% potassium hydroxide solution (0.940 mol) was added to 5.0 kg water and mixed at room temperature until clear. 194.0 g alpha-lipoic acid (99%, 0.931 moles) was added to the potassium hydroxide solution and mixed until clear. 1,046.0 g alpha cyclodextrin (9.25% water content, 0.977 moles) was added and stirred 3 hours until slightly cloudy to clear (in case of the amorphous silica as flowing agent the solution will be slightly cloudy). 0.940 mol of 12 N hydrochloric acid was slowly added until the pH reached pH 3 to precipitate the complex. The final aqueous mixture is spray dried immediately at 180° C.

example 2

Preparation of an Alpha-Lipoic Acid / Alpha Cyclodextrin Complex

[0026] 186.7 g of a 45% potassium hydroxide solution (1.498 moles) was added to 3910 g water and mixed at room temperature until clear. 300 g alpha-lipoic acid (99%, 1.439 moles) was added to the potassium hydroxide solution and mixed until clear clear (in case of the presence of amorphous silica as flowing agent the solution will be slightly cloudy). 1,572 g alpha cyclodextrin (at 9.25% water 1.468 moles) was added and stirred for 3 hours at room temperature until no further clarification was seen. 1.498 moles of 37% hydrochloric acid was added to precipitate the complex. With a minimal molar excess of hydrochloric acid in comparison to the potassium hydroxide used, the final pH of the solution was at pH 3. The final aqueous mixture was spray dried immediately at 180° C.

example 3

Preparation of an Alpha-Lipoic Acid / Alpha Cyclodextrin Complex

[0027] 1.44 moles of potassium hydroxide were added to 5.5 kg of water and mixed at room temperature until clear. The pH of this solution was at pH 14. 300 g alpha-lipoic acid (98%, 1.425 moles) was added to the potassium hydroxide solution and mixed until clear (in case of the presence of amorphous silica as flowing agent the solution will be slightly cloudy). 1.553 kg of dry alpha cyclodextrin (1.598 moles) was added and stirred 50 minutes at room temperature. 1.44 moles of 37% hydrochloric acid was added precipitating the complex. This mixture was stirred 30 minutes at room temperature. The final pH was at about pH 3. This aqueous mixture was spray dried immediately at about 180° C. inlet and about 80° C. outlet temperature.

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Abstract

The invention relates to a process for the preparation of a cyclodextrin / alpha-lipoic acid complex, wherein in a first step, an alpha-lipoic acid and a cyclodextrin are dissolved in an aqueous alkaline solution having a pH above pH 7, and in a second step an acid is added to lower the pH of the solution to a pH below pH 7.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The invention relates to a process for preparing an alpha-lipoic acid / cyclodextrin complex and product prepared. [0003] 2. Background Art [0004] Cyclodextrins are cyclic oligosaccharides composed of 6, 7 or 8 α(1-4)-linked anhydroglucose units. The α-, β- or γ-cyclodextrins, which are prepared for example by enzymatic conversion of starch, differ in the diameter of their hydrophobic cavity and are generally suitable for inclusion of numerous lipophilic substances. [0005] Alpha-lipoic acid (Thioctic Acid) is a naturally occurring molecule produced by both plants and animals. It serves as a cofactor for some enzymes and as an excellent antioxidant / free radical scavenger. Since it has been known that alpha-Lipoic Acid can improve insulin sensitivity in cases of Type II diabetes, alpha-Lipoic Acid has been employed for treating diabetes as well as alcoholic liver disease and other neuropathies. [0006] Alpha-lipoic acid ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/724C08B37/16A61K31/385A23L33/15
CPCA61K31/385A61K31/724A61K47/48969B82Y5/00A61K47/6951A61P1/16A61P3/02A61P3/10A61P5/50A61P25/00A61P39/06
Inventor REUSCHER, HELMUTBAUER, MARK
Owner WACKER CHEM GMBH